Sodium thiopental, a short acting barbiturate, is commonly employed in cardiac surgery as an anesthetic. In order to optimize dosage of this myocardial depressant in patients undergoing cardiopulmonary bypass, we have studied 20 patients and evaluated the influence of hemodilution and hypothermia during the bypass procedure. We quantitated plasma levels of thiopental in patients and kinetically calculated the fraction of drug that is being metabolized hepatically. Although the hepatic extraction and hepatocellular intrinsic clearance are significantly lowered during hypothermic state (temp: 25 degree C) the thiopental levels at the time of taking the aortic clamp off and when the patients is fully rewarmed were not higher than previously observed in non-bypass patients. This is because the decreased metabolism appears to be counter-balanced by increased free fraction due to hemodilution and may be increased partitioning into tissues, e.g., fat. This indicates that no dosage changes may be necessary for anesthetic dose.